Clinical Research On The Involvement Of Intercellular Adhesion Molecule -1 In The Inflammation Of Diabetic Nephropathy

Objectives: To investigate the levels of serum and urinary soluble intercellular adhesion molecule-1(sICAM-1) in different stage of diabetic nephropathy(DN) and their implication; To observe the expression of ICAM-1 in the renal tissue of patients with DN and the change of the renal structure and morphologic in patients with DN; To investigate the effect of Losartan on the level of serum and urinary sICAM-1 in patients with incipient DN.Methods: 12 healthy subjects and 50 patients with type 2 diabetes mellitus(DM) were enrolled in this study,the latter was further divided into three subgroups according to the urinary albumin excretion rate(UAER): 21 patients with normal UAER, 14 patients with microalbuminuria and 15 patients with clinical proteinuria; The patients with microalbuminuria(nonhypertensive) took Losartan 50mg daily for 4 weeks; Serum and urinary sICAM-1 concentrations in the patients and the healthy subjects were measured by enzyme linked immunosorbent assay(ELISA). The expression of ICAM-1 in the renal tissue in patients with DN were detected by immunohistochemical technique. The change of the renal structure and morphologic in patient with DN were observed by light microscopy and electronic microscopy. Results: 1) The levels of serum sICAM-1 and urinary sICAM-1/Cr(creatinine) ratio were significantly higher in patients with type 2 DM than those in normal controls(P<0.01),and increased with increment of UAER; The levels of serum sICAM-1 and urinary sICAM-1/Cr(creatinine) ratio in patients with incipient DN were decreased after taking Losartan for 4 weeks(P<0.05). 2) The levels of serum sICAM-1 were positively correlated with the clinical index such as serum HbA1c,C-reactive protein (CRP),fasting blood glucose (FBG),low density lipoprotein (LDL),serum creatinine (Scr),systolic blood pressure (SBP), (P<0.05或P<0.01). 3) Urinary sICAM-1/Cr ratio were positively correlated with the clinical index such as the level of serum sICAM-1, HbA1c,CRP,FBG,LDL,Scr and SBP(P<0.01). 4) Expression of ICAM-1 in kidney of patients with DN:a diffuse,segmental and strong staining of ICAM-1 was observed at glomeruli.They located mostly in endothelial and mesangial area. The endothelial cells of small artery in the interstitial were positive-stained. The expression of ICAM-1 in the patient with clinical proteinuria was stronger than that in the patient with microalbuminuria.Conclusions:1) The levels of serum and urinary sICAM-1 are increased in the patients with type 2 DM,further increased with the progression of DN,and positively correlated with majority clinical index;The expression of ICAM-1 in renal tissue is increased too. 2) ICAM-1 may involve in the initiation and progression of DN,the change of its concentrations in serum and urine reflects the severity of DN,and relevant to the development of DN; 3) The monitoring of the levels of serum and urinary sICAM-1 is beneficial to the diagnosis of incipient DN. 4) Losartan is a drug in protecting incipient DN, which suggested that Losartan can be served as an anti-inflammatory drug(via inhibiting the expression of ICAM-1)independent of its property—antihypertive.